Intrathecal Trastuzumab for Leptomeningeal Metastases in HER2+ Breast Cancer

NCT ID: NCT01325207

Last Updated: 2019-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-01
• Study Completion Date: 2019-01-20

Brief Summary

The drug being studied is Trastuzumab, a medicine that is used to slow or stop the growth of cancerous tumors that are HER-2 positive. Patients are being asked to participate in this study because they have been diagnosed with having tumor cells in their spinal fluid. This study will investigate the safety and effects of this drug when given directly into the spinal fluid.

Phase I/II Dose Escalation Trial to Assess Safety of Intrathecal Trastuzumab for the Treatment of Leptomeningeal Metastases in HER2 Positive Breast Cancer The purpose of this research study is to determine a safe dose of the drug Trastuzumab and then determine how effective this treatment is.

Detailed Description

Phase I: Patients will be treated in cohorts of 3-6 based on standard phase I dose escalation parameters requiring 0/3 or 1/6 patients per cohort to have a DLT before dose escalation. Dosing is as follows: Cohort 1-10 mg IT, cohort 2-20 mg IT, cohort 3-30 mg IT and cohort 4-40 mg IT. Patients will be treated twice a week for 4 weeks, then once a week for 4 weeks, and then every 2 weeks. Toxicity for DLT will be assessed during first 4 weeks of treatment. Phase II: Patients will be treated with the MTD or maximal defined dose. Patients will be treated twice a week for 4 weeks, then once a week for 4 weeks, and then every 2 weeks.

Conditions

Breast Cancer

Study Design

• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

intravenous trastuzumab infusions

A Phase I single dose study (H0407g) of intravenous trastuzumab infusions ranging from 10-500 mg resulted in dose-dependent pharmacokinetics (PK) with serum clearance of trastuzumab decreasing with an increasing dose at doses \<250 mg. PK modeling of trastuzumab concentration-time data from 7 patients that were administered doses of 250 mg and 500 mg had in a mean halflife of 5.8 days (range 1-32 days).

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: RADIATION

Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks

Interventions

Trastuzumab

Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks

Intervention Type: RADIATION

Other Intervention Names

(also known as Herceptin, which; is a medicine that is used to slow or stop the growth of a cancerous tumor)

Eligibility Criteria

Inclusion Criteria

ELIGIBILITY CRITERIA

• HER2 positive (IHC 3+ and/or FISH positive) breast cancer patients with leptomeningeal metastases by MRI or CSF (if MRI is negative).

o Review will be performed for cases not reviewed at Northwestern for confirmation, but will not preclude patients from entering the trial (pathology report is sufficient for registration).

• Patients can have concomitant brain metastases as long as they do not require active treatment or have been treated.
• Patients with leptomeningeal disease from ependymomas, gliomas, and medulloblastoma will be eligible for phase I
• Life expectancy > 8 weeks
• Normal renal (creatinine < 1.5 ULN), liver (bilirubin < 1.5 x ULN, transaminases < 3.0 x ULN, except in known hepatic metastasis, wherein may be < 5 x ULN) and blood counts (WBC > 3.0, Neutrophils > 1500, platelets >100 000, Hemoglobin > 10).
• LVEF > 50%
• KPS > 50
• Age > 18 years
• Cannot be on systemic agents (chemotherapy) that have CNS penetration unless they develop leptomeningeal metastases while on these agent(s) and have controlled systemic disease. May continue on IV trastuzumab, lapatinib or hormonal agents if controlling systemic disease and developed LM while on therapy. Patients requiring systemic chemotherapy are eligible but will not be able to start treatment until after the first assessment by imaging and cytology.
• Patients may need a CSF flow study at the discretion of the treating principal investigator. If a spinal block is seen by CSF flow study or MRI, it will need local RT prior to treatment. Concurrent radiation is not allowed.
• Patients should be > 2 weeks from RT treatment and all effects of treatment should have resolved
• No limit on prior systemic or IT therapies.
• CSF sampling to document LM if not documented on MRI.
• Must be willing to have an Ommaya reservoir placed.
• NO history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix) unless in complete remission and off all therapy for the disease for a minimum of 3 years.
• Significant medical or psychiatric illness that would interfere with compliance and ability to tolerate treatment as outlined in the protocol.
• Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study.
• Women may not be pregnant or breast-feeding.
• Ability to sign an informed consent; can be signed by family member or health care proxy. Informed consent must be done prior to registration on study.
• All patients must have given signed, informed consent prior to registration on study.
• No known hypersensitivity to trial medications Note: The eligibility criteria listed above are interpreted literally and cannot be waived.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Raizer, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

University of California San Francisco (UCSF)

San Francisco, California, United States

Northwestern University

Chicago, Illinois, United States

Tufts Medical Center

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Columbia University

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Texas Oncology-Austin

Austin, Texas, United States

Countries

United States

References

Malani R, Fleisher M, Kumthekar P, Lin X, Omuro A, Groves MD, Lin NU, Melisko M, Lassman AB, Jeyapalan S, Seidman A, Skakodub A, Boire A, DeAngelis LM, Rosenblum M, Raizer J, Pentsova E. Cerebrospinal fluid circulating tumor cells as a quantifiable measurement of leptomeningeal metastases in patients with HER2 positive cancer. J Neurooncol. 2020 Jul;148(3):599-606. doi: 10.1007/s11060-020-03555-z. Epub 2020 Jun 6.

Reference Type: DERIVED

PMID: 32506369 (View on PubMed)

Other Identifiers

STU00040150

Identifier Type: OTHER

Identifier Source: secondary_id

NU 10C03

Identifier Type: -

Identifier Source: org_study_id